1 in 5 are discharged from hospital with unstable vital signs, and experience higher readmission and death rates Aug 09, 2016

DALLAS – Twenty percent of people hospitalized are released before all vital signs are stable, a pattern that is associated with an increased risk of death and hospital readmission, a new study by UT Southwestern Medical Center researchers shows.

As hospital stays have shortened dramatically over the past 30 years, there is increasing concern that patients are being discharged before all vital signs have stabilized, putting them at risk of adverse events after discharge. However, no studies to date have examined the extent to which patients are discharged with unstable vital signs, and whether this practice is actually associated with higher post-discharge mortality and readmission rates, the researchers said.

“We found that nearly 1 in 5 hospitalized adults is discharged with one or more vital sign instabilities such as an elevated heart rate or low blood pressure,” said lead author, Dr. Oanh Nguyen, Assistant Professor of Internal Medicine and Clinical Sciences. “This finding is an important patient safety issue because patients who had vital sign abnormalities on the day of discharge had higher rates of hospital readmission and death within 30 days even after adjusting for many other risk factors.”

The researchers assessed electronic medical records (EMR) of 32,835 unique individuals from six Dallas-Fort Worth area hospitals, and noted abnormalities in temperature, heart rate, blood pressure, respiratory rate, and oxygen saturation within 24 hours of discharge. Nearly 20 percent had one or more abnormalities, with elevated heart rate being the most common vital sign instability (affecting about 10 percent). About 13 percent were readmitted or died, and individuals with three or more instabilities had a nearly four-fold increase in the odds of death.

“Our findings, that ‘vital signs are still vital’ have important implications for the development of national discharge guidelines to improve patient safety for the 35 million individuals being discharged from hospitals in the U.S. annually,” said co-lead author, Dr. Anil Makam, Assistant Professor of Internal Medicine and Clinical Sciences.        

“At a time when people are developing complicated, black box computerized algorithms to identify patients at high risk of readmission, our study highlights that the stability of vital signs, something doctors review with their own eyes every day, is a simple, clinically objective means of assessing readiness and safety for discharge. There’s a good reason we call them vital signs,” said senior author Dr. Ethan A. Halm, Chief of the William T. and Gay F. Solomon Division of General Internal Medicine, Chief of the Division of Outcomes and Health Services Research in the Department of Clinical Sciences at UT Southwestern, and Director of UT Southwestern’s Center for Patient-Centered Outcomes Research. “It is important for clinicians to look at all of the vital signs in the 24 hours prior to discharge and not just the last set or the best ones in judging a patient’s readiness for discharge.”

Researchers concluded that:

• Discharge guidelines should include objective vital sign criteria for judging stability on discharge to improve disposition planning and post-discharge patient safety.
• At a minimum, patients with one instability on discharge should be discharged with caution.
• Close outpatient follow-up and appropriate patient education about warning signs and symptoms that merit urgent medical attention may be warranted.
• Individuals with two or more instabilities should likely remain in the hospital for continued treatment and observation in the absence of extenuating circumstances.
• Though post-acute care facilities are frequent sites of post-discharge care for those discharged with vital sign instabilities, patients sent to these facilities had still higher rates of readmission and death, suggesting that an alternate site of discharge may have been more appropriate for a significant subset of these individuals.

Other researchers included Dr. Song Zhang, Associate Professor of Clinical Sciences; and researchers from Parkland Health & Hospital System, the Parkland Center for Clinical Innovation (PCCI), and Texas Health Resources.

The study, which appears in the Journal of General Internal Medicine, was supported by grant funding from the Agency for Healthcare Research and Quality, the UT Southwestern Center for Patient-Centered Outcomes Research, the National Institutes of Health, the Commonwealth Foundation, and the UT Southwestern KL2 Scholars Program.

The UT Southwestern Center for Patient-Centered Outcomes Research, led by Dr. Halm, Professor of Internal Medicine and Clinical Sciences, who holds the Walter Family Distinguished Chair in Internal Medicine in Honor of Albert D. Roberts, M.D., is supported by a $5 million grant from the federal Agency for Healthcare Research and Quality and seeks to assess the benefits and harms of different preventive, diagnostic, therapeutic, and health delivery system interventions to inform decision-making, highlighting comparisons and outcomes that matter to people.

The Center works in conjunction with UT Southwestern’s Center for Translational Medicine, part of a $28.6 million grant from the NIH to promote rapid translation of basic laboratory findings into patient care. The Center is a member of a national Clinical and Translational Science Award Consortium that includes more than 60 medical research institutions.

About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year.

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Media Contact: Cathy Frisinger
214-648-3404
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1 in 5 are discharged from hospital with unstable vital signs, and experience higher readmission and death rates Aug 09, 2016

Only 15 percent of preventable spina bifida and anencephaly being prevented worldwide, study finds

Woodruff Health Sciences Center

Approximately only 15 percent of global cases of spina bifida and anencephaly that are preventable through folic acid fortification are actually being prevented according to a study led by epidemiologists and nutrition scientists from the Departments of Epidemiology and Global Health at Emory’s Rollins School of Public Health and the Food Fortification Initiative.

Published in the July edition of Birth Defects Research Part A Clinical and Molecular Teratology, the study emphasizes the preventable morbidity and mortality caused by the lack of cost-effective, easily implementable, and proven strategy of government-required folic acid fortification of food (also termed mandatory fortification). The researchers measured the current status of folic acid-preventable spina bifida and anencephaly (FAP SBA) worldwide. This was particularly significant as it was the 25th anniversary of the Medical Research Council study that proved unequivocally that folic acid prevents a majority of spina bifida and anencephaly.

According to study results, in the year 2015, there were about 35,500 fewer births with spina bifida and anencephaly, a commendable prevention achieved in 58 countries through mandatory folic acid fortification of wheat and maize flour. However, this also points to the urgency of preventing about 233,000 other FAP SBA cases that are still occurring in the remaining countries without effective folic acid interventions, say the authors. Most of Europe, Africa, and Asia is not implementing mandatory fortification with folic acid. Researchers believe that the implementation of mandatory fortification with folic acid offers governments a rapid way to prevent FAP SBA-associated disability and mortality, and to help countries achieve their health-related Sustainable Development Goalsrelated to reduction in infant and under-five mortality.

"No baby in the world should develop preventable birth defects such as FAP SBA and congenital rubella syndrome, because we have a known preventable strategy to aid against these conditions," says Dr. Godfrey P. Oakley Jr., MD, a pediatrician and the director of the Center for Spina Bifida Prevention at Emory’s Rollins School of Public Health. "Ignoring a preventable strategy for preventing serious birth defects can be compared to having a vaccine for Zika virus and not using it."

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Melva Robertson
404-727-5692
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Only 15 percent of preventable spina bifida and anencephaly being prevented worldwide, study finds

Surgical removal of the thymus benefits myasthenia gravis patients without a chest tumor, according to NEJM paper

First-ever randomized study of thymectomy was led by faculty member at Jacobs School of Medicine and Biomedical Sciences at UB

BUFFALO, N.Y. –- A new study in the New England Journal of Medicine addresses a question doctors have sought to clarify for decades: whether a surgery conducted since the 1940s benefits the patients it targets.

The study to be published August 11 (available online on August 10 at 5 p.m.) found that surgical removal of the thymus gland from patients with myasthenia gravis, a rare autoimmune disease that affects neuromuscular function, provides significant benefit in patients who do not have a chest tumor.

Myasthenia gravis (MG) results from an immune-mediated disruption of communication between nerve and muscle – the neuromuscular junction. Symptoms may include droopy eyelids; blurred or double vision; difficulty speaking, swallowing and breathing; and muscle weakness. Some patients develop thymoma, a benign tumor of the thymus gland. The disease affects as many as 60,000 Americans and its incidence has been increasing, in part as a result of improved diagnostic techniques and an aging population.

The new study provides a definitive answer that neurologists have sought for decades, according to Gil I. Wolfe, MD, Irvin and Rosemary Smith Chair of the Department of Neurology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, clinical chair of the worldwide study and first author.

Solid confirmation

“These findings solidly confirm the early use of thymectomy in managing myasthenia gravis,” he said. “These findings tell patients they can be even more assured that thymectomy is a positive step to take in the management of their condition.”

Since the 1940s, thymectomy has been used in MG patients, both in patients with a chest tumor called thymoma and those without. Wolfe said it is widely accepted that patients with a thymoma need to have it surgically removed. But the data have not been as clear in MG patients who do not present with a tumor.

“Until this study, the only evidence was from non-randomized studies that contained significant bias issues,” said Wolfe, an expert on neuromuscular disorders with a special focus on MG, who was awarded the 2015 Doctor of the Year award from the Myasthenia Gravis Foundation of America. Wolfe sees patients through UBMD Neurology at Buffalo General Medical Center.

Around 2000, when he was at the University of Texas Southwestern, Wolfe worked with colleagues in the field, John Newsom-Davis, MD; Henry Kaminski, MD; Fred Jaretzki, MD and Gary D. Cutter, PhD, to develop a study that would provide the data that neurologists needed to correctly assess the value of thymectomy.

The global study is the longest and one of the largest randomized studies in the history of MG. It ran from 2006 until 2012 with 126 patients with MG who participated in centers located on almost every continent. It judged the effectiveness of thymectomy by comparing disease status of patients and how much of the corticosteroid prednisone they needed after the surgery compared to patients who did not have surgery.

Less prednisone

The study found that thymectomy patients needed approximately one-third less prednisone to control their disease than did those who did not have the surgery. Their need for steroid-sparing immunosuppresants, such as azathioprine, was reduced by nearly two-thirds.

Wolfe said: “We were quite satisfied to see that thymectomy conferred benefits on disease status measures by the Quantitative Myasthenia Gravis (QMG) score, reduced the need for corticosteroids and other immunosuppressants, reduced hospitalization needs, and also, according to most measures, reduced the side effect burden.”

Only a few decades ago, approximately a third of all patients with MG died from it, but new diagnostic techniques and treatments have dramatically improved both the quality of life and longevity of patients. Today, the lifespan for myasthenia gravis patients matches that of the general population.

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Surgical removal of the thymus benefits myasthenia gravis patients without a chest tumor, according to NEJM paper

Research suggests new tool for cancer treatment based on cell type

WEST LAFAYETTE, Ind. – A new tumor model has been shown to predict how certain types of cancer cells react differently to a commonly used chemotherapy drug, a potential tool for "precision medicine," in which drug treatment is tailored to individual patients and certain cancer types.

Drug resistance and various subtypes of tumors represent critical bottlenecks for effective chemotherapy.

"This means rapid and accurate screening of effective drugs and drug combinations can be extremely useful to realize precision medicine for cancer therapy," said Bumsoo Han, a Purdue University professor of mechanical and biomedical engineering

Recent research findings demonstrate that a new tumor-modeling platform called a tumor-microenvironment-on-chip (T-MOC) can be used to visualize and quantify how different types of cancer cells react differently to the chemotherapy drug doxorubicin. The drug sometimes failed during testing to kill cancer cells yet stopped their growth.

"So, there are differences in the response to the drug based on cancer type," Han said. "Our platform makes it possible to assess the efficacy of chemotherapeutic drugs according to cell-type; for example, which cells actually died from this drug, which cells didn't die but stopped actively growing, or even which cells survived the drug."

Based on experimental data, the researchers developed a theoretical model to quantify and ultimately predict the effectiveness of drugs depending on the type of cancer cell being treated.

The findings were detailed in a paper published in the July issue of Molecular Pharmaceutics. The paper was authored by graduate student Kyeonggon Shin, undergraduate Brett S. Klosterhoff and Han.

Researchers performed experiments using the T-MOC platform that could help usher in precision medicine, in which drug treatment is tailored to specific patients and certain cell types.

"We are providing a new tool, a new platform to test drugs and drug delivery systems for precision medicine," Han said.

The device is about 4.5 centimeters (1.8 inches) square and contains "microfluidic" channels where cancer cells were cultured within a three-dimensional "extracellular matrix," a scaffold-like material found between cells in living tissue. The experiments also incorporated "interstitial fluid," which is found inside tumors and is thought to be a barrier to drug delivery.

Three types of human breast cancer cell lines were cultured on the T-MOC platform, and their drug response and resistance to doxorubicin were characterized by time-lapse fluorescence microscopy.

"Particularly in breast cancer, there are different subgroups of cancers," Han said. "Depending on the subgroup, the drug response is different. So, to study the efficacy of a drug and its nanoparticle formulation, we examined how the drug and nanoparticles were transported through the interstitial space and uptaken by different types of cancer cells."

Two of the three types of breast cancer cells tested were triple negative breast cancer, one of the most-difficult-to-treat forms of the disease.

"Even within triple negative there are additional subtypes, so this is not one single disease," Han said. "The targeting drugs only work with certain types of cells."

The findings also showed some cell types take up drugs more rapidly than others.

"You can see that, depending on the cell type, the response to the same drug is different and the drug uptake is different," he said.

Future research will involve comparing and validating research results with data from laboratory animal tests and incorporating a more complex mixture of tumor stromal components in the T-MOC experiments. Ultimately, in precision medicine, a patient's tumor cells might be studied using a T-MOC system to determine the proper drug and dosage to use before beginning treatment, Han said.

Research to fabricate the microfluidic device was performed at the Birck Nanotechnology Center in Purdue's Discovery Park. The work also is associated with the Purdue University Center for Cancer Research.

The research was partially funded by the National Institutes of Health; a Collaboration in Translational Research Award from the Indiana Clinical and Translational Sciences Institute; the Walther Cancer Foundation; and the Digital Human Project. 

Writer: Emil Venere, 765-494-4709, [email protected] 

Source: Bumsoo Han, 765-494-5626, [email protected]

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ABSTRACT

Characterization of Cell-Type-Specific Drug Transport and Resistance of Breast Cancers Using Tumor-Microenvironment-on-Chip       

Kyeonggon Shin,^† Brett S. Klosterhoff,^† and Bumsoo Han^*

^†School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907, United States ^§Weldon School of Biomedical Engineering, Birck Nanotechnology Center, and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States ^* Corresponding author, e-mail [email protected]    

Heterogeneous response and resistance of cancer cells to chemotherapeutic drugs pose a significant challenge for successful cancer treatments. In this study, an integrated experimental and theoretical analysis of cellular drug transport was developed. The experimental platform, called tumor-microenvironment-on-chip (T-MOC), is a microfluidic platform where cancer cells were cultured within a three-dimensional extracellular matrix perfused with interstitial fluid. Three types of human breast cancer cell lines (MCF-7, MDA-MB-231, and SUM-159PT) were cultured on this T-MOC platform, and their drug response and resistance to doxorubicin were characterized by time-lapse quantitative fluorescence microscopy. To study the effects of nanoparticle-mediated drug delivery, the transport and action of doxorubicin encapsulated nanoparticles were also examined. Based on the experimental data obtained, a theoretical model was developed to quantify and ultimately predict the cellular transport processes of drugs cell-type specifically. The results demonstrate that the cellular drug transport can be celltype-specifically quantified by rate constants representing the uptake and efflux of doxorubicin across the cellular membrane.

 

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Infant gut microbiota linked to milk allergy resolution

Cow’s milk allergy is the most common food allergy in young children, affecting 2-3%. A child may have to live with the limitations imposed by milk allergy for several years, as recent studies have shown that milk allergy often continues into later childhood and adulthood. Parents of milk allergic children often ask allergists to gauge whether their child’s milk allergy will resolve. The etiology and course of food allergy may involve deviation from immune tolerance that is driven by diet, commensal microbiota, and interactions between them. Previous work in this area has relied upon culture methods, which allow for examination of species specifically targeted and cultured, but exclude the large majority of bacterial organisms that cannot be cultured. These excluded organisms may play key roles in the natural history of milk allergy.

In a recent article published in The Journal of Allergy and Clinical Immunology (JACI) Bunyavanich and colleagues addressed the hypothesis that gut microbiota play a role in the natural history of milk allergy.  Bunyavanich and colleagues used high-throughput sequencing to comprehensively characterize the infant gut microbiota of 226 children age 3-16 months with cow’s milk allergy. Their use of high-throughput sequencing allowed them to systematically profile bacterial taxa in the infant gut environment, including the vast majority that cannot be cultured. The research team followed these children up to age 8 years, finding that 56.6% of them outgrew their milk allergy. They used computational biology approaches to examine for links between early-life gut microbiota diversity, composition, and milk allergy resolution.

Dr. Bunyavanich and her colleagues found enrichment of specific bacterial taxa-- Clostridia and Firmicutes-- in the infant gut microbiome of 3-6 month old subjects whose milk allergy resolved by age 8 years. The microbiota of these young infants whose milk allergy resolved were associated with decreased fatty acid metabolism. The team’s results are the first to address the relationship between gut microbiota and food allergy resolution. Their findings suggest directions for prospective examination of the identified microbiota for potential therapeutic consideration. Early infancy may be an important window during which gut microbiota shape food allergy outcomes.

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

American Academy of Allergy, Asthma & Immunology

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Infant gut microbiota linked to milk allergy resolution

New model sheds light on secondary bacterial pneumonia

Research could pave way to prevent secondary infections in people with influenza A virus

BUFFALO, N.Y. – For years, researchers have known that the bacteria Staphylococcus aureus (S. aureus) can trigger severe, sometimes deadly, secondary bacterial pneumonia in some people who are subsequently infected with influenza A virus, but scientists have not known exactly how this happens.

Now, University at Buffalo scientists have developed a new model for studying this phenomenon, which could lead to new ways to prevent secondary bacterial infections. The findings were published this week in mBio, an online open-access journal of the American Society for Microbiology.

“This study has established a physiologically relevant model, so we can now more carefully evaluate the actual events involved after colonization with S. aureus and identify the primary factors that can lead to secondary bacterial pneumonia,” said Anthony Campagnari, PhD, senior author and professor in the Department of Microbiology and Immunology and the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB.

S. aureus is one of the most common causes of secondary bacterial pneumonia in cases of seasonal influenza. Scientists have been studying this phenomenon by introducing S. aureus directly into the lungs of mice. However, this does not mimic the natural pathogenesis of infection.

In the new model, Ryan Reddinger, a doctoral candidate in the UB Department of Microbiology and Immunology who is working in Campagnari’s lab, developed a technique where S. aureus stably colonizes the nares (nostrils) of mice and these animals are subsequently infected with influenza A virus to see what would happen.

“Ryan’s work demonstrated that influenza A virus infection leads to the dissemination of S. aureus from the nasal cavity into the lungs, resulting in the development of secondary bacterial pneumonia in these mice,” said Campagnari. “The model is very relevant to the current physiologic state in humans where individuals are colonized by S. aureus in the nares and subsequently acquire a viral infection.

“The fascinating thing about this model is when we colonize mice with S. aureus it remains in the nares for up to seven days, without obvious signs of disease and does not appear to move to the lungs on its own,” Campagnari noted. “The bacteria only disseminates to the lungs in response to the subsequent viral infection.”

When someone has a viral infection, certain physiologic changes occur in the nasopharynx that are related to damage of host cells and host responses, including increased body temperature and release of glucose, norepinephrine and the cellular energy carrier, adenosine triphosphate or ATP. With their model, the UB researchers discovered that a combination of these factors, in the absence of influenza A virus, will cause S. aureus to leave the nasopharynx and travel to the lungs.

“We don’t know why the viral infection induces the bacteria to disseminate to the lung, but now we can evaluate potential mechanisms more closely because of this model,” said Campagnari. “In addition, this model could be adapted to study other virus-bacterial interactions.”

Founded in 1846, the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo is beginning a new chapter in its history with the largest medical education building under construction in the nation. The eight-story, 628,000-square-foot facility is scheduled to open in 2017. The new location puts superior medical education, clinical care and pioneering research in close proximity, anchoring Buffalo’s evolving comprehensive academic health center in a vibrant downtown setting. These new facilities will better enable the school to advance health and wellness across the life span for the people of New York and the world through research, clinical care and the education of tomorrow’s leaders in health care and biomedical sciences. The school’s faculty and residents provide care for the community’s diverse populations through strong clinical partnerships and the school’s practice plan, UBMD Physicians’ Group.

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New model sheds light on secondary bacterial pneumonia

Peanut allergy prevention strategy does not impact growth or nutrition

The primary results of the LEAP trial, published in 2015 showed that consumption of peanut from infancy led to an 81 percent relative reduction in subsequent development of the allergy compared to avoiding peanut altogether. Although an effective strategy for the prevention of peanut allergy in high-risk infants, regular peanut consumption from infancy and throughout early childhood could have unexpected consequences for growth and nutrition.

In a recent paper published in The Journal of Allergy and Clinical Immunology (JACI) Feeney and colleagues report secondary results from the LEAP Study.

The original LEAP trial randomly assigned 640 infants aged 4 to 11 months to regularly consume at least 6g peanut protein per week or to avoid peanut until 5 years of age. In this publication, the researchers report on the feasibility of regular consumption of peanut products from infancy and whether this dietary intervention would have any adverse effects on infant and child growth and nutrition. Adherence to peanut consumption or avoidance advice was assessed by dietary questionnaires; nutritional intake assessed from three day prospective food diaries and growth evaluated from anthropometric measurements (weight, height, body mass index, waist circumference and skinfold thickness) recorded at regular clinic visits.

The study found that peanut consumers easily achieved the recommended weekly peanut intake, consuming 7.5 grams weekly on average. Importantly, the introduction of peanut in breast-feeding infants did not affect the duration of breast-feeding. They did not observe any differences for measures of infant and child growth between the peanut consumers and avoiders at any point during the study, even when comparing the subgroup of children with the highest peanut intakes with those who avoided peanut. There were no differences in energy (calorie) and protein intakes, although consumers had higher fat intakes and avoiders had higher carbohydrate intakes; these differences were greatest for the subgroup of children with the highest peanut intakes. Sodium (salt) intakes were above recommended intakes in both groups, there were no differences between intakes for consumers compared to avoiders. There were also no differences for intakes of micronutrients such as calcium, iron, zinc and vitamin D. The children in the consumption group made some different food choices to the avoiders. Peanut products appeared to be eaten instead of foods such as crisps and savoury snacks, high fibre bread, fruit juice & smoothies and spreads.

Introduction of peanut proved feasible in infants at high risk of peanut allergy and did not affect the duration of breast-feeding nor impact negatively on growth or nutrition. Energy balance was achieved in both groups through variations in intakes from fat and carbohydrate while protein homeostasis was maintained.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

American Academy of Allergy, Asthma & Immunology

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Peanut allergy prevention strategy does not impact growth or nutrition